Navigation of brain networks

Understanding the mechanisms of neural communication in large-scale brain networks remains a major goal in neuroscience. We investigated whether navigation is a parsimonious routing model for connectomics. Navigating a network involves progressing to the next node that is closest in distance to a desired destination. We developed a measure to quantify navigation efficiency and found that connectomes in a range of mammalian species (human, mouse and macaque) can be successfully navigated with near-optimal efficiency (>80% of optimal efficiency for typical connection densities). Rewiring network topology or repositioning network nodes resulted in 45%-60% reductions in navigation performance. Specifically, we found that brain networks cannot be progressively rewired (randomized or clusterized) to result in topologies with significantly improved navigation performance. Navigation was also found to: i) promote a resource-efficient distribution of the information traffic load, potentially relieving communication bottlenecks; and, ii) explain significant variation in functional connectivity. Unlike prevalently studied communication strategies in connectomics, navigation does not mandate biologically unrealistic assumptions about global knowledge of network topology. We conclude that the wiring and spatial embedding of brain networks is conducive to effective decentralized communication. Graph-theoretic studies of the connectome should consider measures of network efficiency and centrality that are consistent with decentralized models of neural communication

Comparative Connectomics.

We introduce comparative connectomics, the quantitative study of cross-species commonalities and variations in brain network topology that aims to discover general principles of network architecture of nervous systems and the identification of species-specific features of brain connectivity. By comparing connectomes derived from simple to more advanced species, we identify two conserved themes of wiring: the tendency to organize network topology into communities that serve specialized functionality and the general drive to enable high topological integration by means of investment of neural resources in short communication paths, hubs, and rich clubs. Within the space of wiring possibilities that conform to these common principles, we argue that differences in connectome organization between closely related species support adaptations in cognition and behavior.We thank Lianne Scholtens, Jim Rilling, Tom Schoenemann for discussions and comments. MPvdH was supported by a VENI (# 451-12-001) grant from the Netherlands Organization for Scientific Research (NWO) and a Fellowship of MQ.This is the author accepted manuscript. The final version is available from Elsevier via https://doi.org/10.1016/j.tics.2016.03.00

The role of symmetry in neural networks and their Laplacian spectra

Human and animal nervous systems constitute complexly wired networks that form the infrastructure for neural processing and integration of information. The organization of these neural networks can be analyzed using the so-called Laplacian spectrum, providing a mathematical tool to produce systems-level network fingerprints. In this article, we examine a characteristic central peak in the spectrum of neural networks, including anatomical brain network maps of the mouse, cat and macaque, as well as anatomical and functional network maps of human brain connectivity. We link the occurrence of this central peak to the level of symmetry in neural networks, an intriguing aspect of network organization resulting from network elements that exhibit similar wiring patterns. Specifically, we propose a measure to capture the global level of symmetry of a network and show that, for both empirical networks and network models, the height of the main peak in the Laplacian spectrum is strongly related to node symmetry in the underlying network. Moreover, examination of spectra of duplication-based model networks shows that neural spectra are best approximated using a trade-off between duplication and diversification. Taken together, our results facilitate a better understanding of neural network spectra and the importance of symmetry in neural networks

Impaired Structural Motor Connectome in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease selectively affecting upper and lower motor neurons. Patients with ALS suffer from progressive paralysis and eventually die on average after three years. The underlying neurobiology of upper motor neuron degeneration and its effects on the complex network of the brain are, however, largely unknown. Here, we examined the effects of ALS on the structural brain network topology in 35 patients with ALS and 19 healthy controls. Using diffusion tensor imaging (DTI), the brain network was reconstructed for each individual participant. The connectivity of this reconstructed brain network was compared between patients and controls using complexity theory without - a priori selected - regions of interest. Patients with ALS showed an impaired sub-network of regions with reduced white matter connectivity (p = 0.0108, permutation testing). This impaired sub-network was strongly centered around primary motor regions (bilateral precentral gyrus and right paracentral lobule), including secondary motor regions (bilateral caudal middle frontal gyrus and pallidum) as well as high-order hub regions (right posterior cingulate and precuneus). In addition, we found a significant reduction in overall efficiency (p = 0.0095) and clustering (p = 0.0415). From our findings, we conclude that upper motor neuron degeneration in ALS affects both primary motor connections as well as secondary motor connections, together composing an impaired sub-network. The degenerative process in ALS was found to be widespread, but interlinked and targeted to the motor connectome

Fluctuations between high- and low-modularity topology in time-resolved functional connectivity

Modularity is an important topological attribute for functional brain networks. Recent studies have reported that modularity of functional networks varies not only across individuals being related to demographics and cognitive performance, but also within individuals co-occurring with fluctuations in network properties of functional connectivity, estimated over short time intervals. However, characteristics of these time-resolved functional networks during periods of high and low modularity have remained largely unexplored. In this study we investigate spatiotemporal properties of time-resolved networks in the high and low modularity periods during rest, with a particular focus on their spatial connectivity patterns, temporal homogeneity and test-retest reliability. We show that spatial connectivity patterns of time-resolved networks in the high and low modularity periods are represented by increased and decreased dissociation of the default mode network module from task-positive network modules, respectively. We also find that the instances of time-resolved functional connectivity sampled from within the high (low) modularity period are relatively homogeneous (heterogeneous) over time, indicating that during the low modularity period the default mode network interacts with other networks in a variable manner. We confirmed that the occurrence of the high and low modularity periods varies across individuals with moderate inter-session test-retest reliability and that it is correlated with previously-reported individual differences in the modularity of functional connectivity estimated over longer timescales. Our findings illustrate how time-resolved functional networks are spatiotemporally organized during periods of high and low modularity, allowing one to trace individual differences in long-timescale modularity to the variable occurrence of network configurations at shorter timescales.Comment: Reorganized the paper; to appear in NeuroImage; arXiv abstract shortened to fit within character limit

Discordant attributes of structural and functional brain connectivity in a two-layer multiplex network.

Several studies have suggested that functional connectivity (FC) is constrained by the underlying structural connectivity (SC) and mutually correlated. However, not many studies have focused on differences in the network organization of SC and FC, and on how these differences may inform us about their mutual interaction. To explore this issue, we adopt a multi-layer framework, with SC and FC, constructed using Magnetic Resonance Imaging (MRI) data from the Human Connectome Project, forming a two-layer multiplex network. In particular, we examine node strength assortativity within and between the SC and FC layer. We find that, in general, SC is organized assortatively, indicating brain regions are on average connected to other brain regions with similar node strengths. On the other hand, FC shows disassortative mixing. This discrepancy is apparent also among individual resting-state networks within SC and FC. In addition, these patterns show lateralization, with disassortative mixing within FC subnetworks mainly driven from the left hemisphere. We discuss our findings in the context of robustness to structural failure, and we suggest that discordant and lateralized patterns of associativity in SC and FC may provide clues to understand laterality of some neurological dysfunctions and recovery

Impaired Cerebellar Functional Connectivity in Schizophrenia Patients and Their Healthy Siblings

The long-standing notion of schizophrenia as a disorder of connectivity is supported by emerging evidence from recent neuroimaging studies, suggesting impairments of both structural and functional connectivity in schizophrenia. However, investigations are generally restricted to supratentorial brain regions, thereby excluding the cerebellum. As increasing evidence suggests that the cerebellum contributes to cognitive and affective processing, aberrant connectivity in schizophrenia may include cerebellar dysconnectivity. Moreover, as schizophrenia is highly heritable, unaffected family members of schizophrenia patients may exhibit similar connectivity profiles. The present study applies resting-state functional magnetic resonance imaging to determine cerebellar functional connectivity profiles, and the familial component of cerebellar connectivity profiles, in 62 schizophrenia patients and 67 siblings of schizophrenia patients. Compared to healthy control subjects, schizophrenia patients showed impaired functional connectivity between the cerebellum and several left-sided cerebral regions, including the hippocampus, thalamus, middle cingulate gyrus, triangular part of the inferior frontal gyrus, supplementary motor area, and lingual gyrus (all p < 0.0025, whole-brain significant). Importantly, siblings of schizophrenia patients showed several similarities to patients in cerebellar functional connectivity, suggesting that cerebellar dysconnectivity in schizophrenia might be related to familial factors. In conclusion, our findings suggest that dysconnectivity in schizophrenia involves the cerebellum and that this defect may be related to the risk to develop the illness

Fixed priority scheduling with pre-emption thresholds and cache-related pre-emption delays: integrated analysis and evaluation

Commercial off-the-shelf programmable platforms for real-time systems typically contain a cache to bridge the gap between the processor speed and main memory speed. Because cache-related pre-emption delays (CRPD) can have a significant influence on the computation times of tasks, CRPD have been integrated in the response time analysis for fixed-priority pre-emptive scheduling (FPPS). This paper presents CRPD aware response-time analysis of sporadic tasks with arbitrary deadlines for fixed-priority pre-emption threshold scheduling (FPTS), generalizing earlier work. The analysis is complemented by an optimal (pre-emption) threshold assignment algorithm, assuming the priorities of tasks are given. We further improve upon these results by presenting an algorithm that searches for a layout of tasks in memory that makes a task set schedulable. The paper includes an extensive comparative evaluation of the schedulability ratios of FPPS and FPTS, taking CRPD into account. The practical relevance of our work stems from FPTS support in AUTOSAR, a standardized development model for the automotive industry

Multiscale examination of cytoarchitectonic similarity and human brain connectivity

The human brain comprises an efficient communication network, with its macroscale connectome organization argued to be directly associated with the underlying microscale organization of the cortex. Here, we further examine this link in the human brain cortex by using the ultrahigh-resolution BigBrain dataset; 11,660 BigBrain profiles of laminar cell structure were extracted from the BigBrain data and mapped to the MRI based Desikan–Killiany atlas used for macroscale connectome reconstruction. Macroscale brain connectivity was reconstructed based on the diffusion-weighted imaging dataset from the Human Connectome Project and cross-correlated to the similarity of laminar profiles. We showed that the BigBrain profile similarity between interconnected cortical regions was significantly higher than those between nonconnected regions. The pattern of BigBrain profile similarity across the entire cortex was also found to be strongly correlated with the pattern of cortico-cortical connectivity at the macroscale. Our findings suggest that cortical regions with higher similarity in the laminar cytoarchitectonic patterns have a higher chance of being connected, extending the evidence for the linkage between macroscale connectome organization and microscale cytoarchitecture. The human brain connectome organization has been suggested to associate with cytoarchitecture similarity. Here, we utilize the state-of-the-art ultrahigh-resolution BigBrain dataset and diffusion-weighted imaging dataset to examine this association. Our results show that cortical regions with higher cytoarchitecture similarity are more likely to be connected, as well as connected by stronger white matter tracts. This work further extends our understanding of the interaction between macroscale cortico-cortical connectivity organization and microscale cortical cytoarchitecture